A self-limiting switch based on translational control regulates the transition from proliferation to differentiation in an adult stem cell lineage.
A self-limiting switch based on translational control regulates the transition from proliferation to differentiation in an adult stem cell lineage.
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DOI：
10.1016/j.stem.2012.08.012
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发表时间：
2012-11-02
期刊：
影响因子：
23.9
通讯作者：
Fuller, Margaret T.
中科院分区：
文献类型：
--
作者：
Insco, Megan L.;Bailey, Alexis S.;Kim, Jongmin;Olivares, Gonzalo H.;Wapinski, Orly L.;Tam, Cheuk Ho;Fuller, Margaret T.
在成体干细胞谱系中，祖细胞通常在终末分化之前经历有丝分裂转运扩增（TA）分裂，从而允许每次干细胞分裂产生许多分化的后代。限制TA分裂并触发向分化的转换的机制可以通过防止致癌突变在增殖群体中的积累来防止癌症。在这里，我们表明果蝇雄性生殖干细胞谱系从TA增殖到分化的转换是由翻译控制介导的。TRIM-NHL肿瘤抑制同源物Mei-P26促进分化调节剂Bam在TA细胞中的积累。反过来，Bam及其配偶体Bgcn结合mei-P26 3′UTR并抑制晚期TA细胞中mei-P26的翻译。因此，生殖细胞通过不同的顺序调节状态进行，从Mei-P26 on/Bam off到Bam on/Mei-P26 off。跨物种的TRIM-NHL同源物促进从增殖到分化的转换，这表明了一种新的和保守的发育程序性肿瘤抑制机制。
In adult stem cell lineages, progenitor cells commonly undergo mitotic transit amplifying (TA) divisions before terminal differentiation, allowing production of many differentiated progeny per stem cell division. Mechanisms that limit TA divisions and trigger the switch to differentiation may protect against cancer by preventing accumulation of oncogenic mutations in the proliferating population. Here we show that the switch from TA proliferation to differentiation in the Drosophila male germline stem cell lineage is mediated by translational control. The TRIM-NHL tumor suppressor homolog Mei-P26 facilitates accumulation of the differentiation regulator Bam in TA cells. In turn, Bam and its partner Bgcn bind the mei-P26 3′UTR and repress translation of mei-P26 in late TA cells. Thus, germ cells progress through distinct, sequential regulatory states, from Mei-P26 on/Bam off to Bam on/Mei-P26 off. TRIM-NHL homologs across species facilitate the switch from proliferation to differentiation, suggesting a novel and conserved developmentally-programmed tumor suppressor mechanism.
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